A primary objective relates to detection and in situ characterization of biochemically unfamiliar macromolecules, such as mucosubstances and basic proteins in certain sites. The relationship of these substances to known enzymes, as for example, the possible association of acid mucosubstances and lysosomal enzymes in a number of sites may clarify certain cellular mechanisms at the molecular level. Moreover, insight into the function of particular cells or cell structures will be sought from correlated ultrastructural, cytochemical and biochemical investigations. Such correlated investigations indicate heterogeneity of lysosome-like organelles in some sites such as human placenta, for example. Such heterogeneity may reflect either the presence of different types of cell organelles or the occurrence of a single organelle in different stages of activity. Another objective of the program involves localization of known biochemical components, including enzymes, glycoproteins and specific receptors on cell surfaces in studies aimed at relating cell surface activities to structure and chemistry. Finally, the contemplated research will undertake to apply new knowledge of cell biology to investigation of pathogenesis of lesions in certain diseases. As an example, current studies inquire into the mechanism whereby vacuolization develops in sweat glands of patients with Hurler's Disease, seeking to determine whether the current view of these vacuoles as secondary lysosomes with stored material adequately explains the ultrastructural findings.